Conceptualizations of childhood, pedagogy and educational research in the postmodern : A critical interpretation

Over the last fifty years the debate between modernism and postmodernism has surfaced in the disciplines of social sciences. Epistemologically, there is a shift away from the concept of a “found” world, “out there”, objective, knowable and factual, towards a concept of “constructed” worlds, thus problematizing postulates based on the autonomous, stable, unified, essentialized, coherent and integrated subject capable of rational action, and opening up spaces for a new understanding of subjectivity that is based on provisionality and contingency. From the ashes of these tendencies for fragmentation has arisen what is called the New Sociology of Childhood and the new directions in pedagogy and research creating new spaces for constructing notions of children and childhoods. The emergent child has an active agency making it possible to construct a more dynamic child, located in a multiplicity of domains, thus opening up spaces for more flexible pedagogies and new sensibilities in educational research. I have therefore undertaken a critical reading of texts in the area of childhood, pedagogy and educational research within the modern and the postmodern in order to extract, appropriate and integrate parallel but socially constructed discourses across disciplines such as Sociology of Childhood, Sociology of Knowledge and Sociology of Education. I aim to reconstruct the concept of childhood both historically and within modernist/ postmodernist paradigm. I finally try to sift out and document some of the implications for study of childhood, as well as for pedagogical practices and educational research resulting from the paradigmatic shift from modernity to postmodernity. Finally postmodern constructs are problematized and a critical postmodernist position is invoked in order to straddle progressive aspects of modernity and postmodernity

Structuring of Modern and Postmodern Identities with Reflections on the Pedagogical Implications in a Multicultural World

This essay explores the different discourses that intersect to define and explain the concept of "identity" and consists of two distinct parts. The former being an attempt to eclecticize the discourses around identity and the structuring of identity under modern and post-modern conditions. The latter consisting of reflections on the methodological and pedagogical implications in a fragmenting postmodern and multicultural condition. This essay is a theoretical attempt to deconstruct the notion of the essentialized, stable, static and coherent modernist subjectivity/identity and tries to explore the construction of a multilayered, non-unitary, fragmented, plural postmodern subjectivity/identity. The essay aims to discusses the current politics of `identity´, `difference´, `recognition´ and `multiculturalism´ and explores the intricate enmeshing of concepts such as identity, ethnicity, minorities and nationalism. It further tries to construct the representation of identities within a world-systems paradigm. Modernity is seen as being convergent and a result of capital accumulation resulting in globalisation. Post-modernity is seen as a condition of fragmentation due to capital flight, resulting in discontinuities between different forms of collective and individual life. The deconstruction of modernist identity has methodological and pedagogical implications. This fragmentation and disintegration of stable hegemony has emancipatory potential within research. It has led to the decline of writing the "Other". Writing the "Other" is seen as a violence, as it silences and disallows the other from representing themselves. Mere ethnographic observation needs to give way to a dialogic methodology. This has resulted in a focus in research on self-definition, self-identification, autobiographical and local narratives and a replacement of flawed grand narratives. It has also led to a new awareness of pluralism and diversity and articulation of a cultural politics in which culture is bound up with power and resistance. Feminist identity perspectives have strengthened research methodologies by creating empowering and self-reflexive research designs - concerned with producing emancipatory knowledge and empowering the researched. Pedagogically, from the perspective of postmodernism, modernist authority privileges western patriarchal culture and represses and marginalizes the voices of the subordinated. Hence the essay suggests the need for practicing "critical pedagogy" that views education as a political, social and cultural enterprise, and "border pedagogy" that incorporates the notion of difference as an ideal. In practice the culturally divergent fragmented postmodern condition calls for advocating policies of multiculturalism and multiligualism in education

Picking Pyknons out of the Human Genome

In a recent paper in PNAS, Rigoutsos et al. (2006) describe a nonrandom pattern of repeated elements, called pyknons, which are found more frequently in the 3′ untranslated regions of genes than in other regions of the human genome. Although it is unclear how pyknons might have arisen, it is possible that they may be involved in a new form of gene regulation

Regionally enriched rare deleterious exonic variants in the UK and Ireland

It is unclear how patterns of regional genetic differentiation in the UK and Ireland might impact the protein-coding fraction of the genome. We exploit UK Biobank (UKB) and Viking Genes whole exome sequencing data to study regional genetic differentiation across the UK and Ireland in protein coding genes, encompassing 44,696 unrelated individuals from 20 regions of origin. We demonstrate substantial exonic differentiation among Shetlanders, Orcadians, individuals with full or partial Ashkenazi Jewish ancestry and in several mainland regions (particularly north and south Wales, southeast Scotland and Ireland). With stringent filtering criteria, we find 67 regionally enriched (≥5-fold) variants likely to have adverse biomedical consequences in homozygous individuals. Here, we show that regional genetic variation across the UK and Ireland should be considered in the design of genetic studies and may inform effective genetic screening and counselling

Variant detection sensitivity and biases in whole genome and exome sequencing

BACKGROUND: Less than two percent of the human genome is protein coding, yet that small fraction harbours the majority of known disease causing mutations. Despite rapidly falling whole genome sequencing (WGS) costs, much research and increasingly the clinical use of sequence data is likely to remain focused on the protein coding exome. We set out to quantify and understand how WGS compares with the targeted capture and sequencing of the exome (exome-seq), for the specific purpose of identifying single nucleotide polymorphisms (SNPs) in exome targeted regions. RESULTS: We have compared polymorphism detection sensitivity and systematic biases using a set of tissue samples that have been subject to both deep exome and whole genome sequencing. The scoring of detection sensitivity was based on sequence down sampling and reference to a set of gold-standard SNP calls for each sample. Despite evidence of incremental improvements in exome capture technology over time, whole genome sequencing has greater uniformity of sequence read coverage and reduced biases in the detection of non-reference alleles than exome-seq. Exome-seq achieves 95% SNP detection sensitivity at a mean on-target depth of 40 reads, whereas WGS only requires a mean of 14 reads. Known disease causing mutations are not biased towards easy or hard to sequence areas of the genome for either exome-seq or WGS. CONCLUSIONS: From an economic perspective, WGS is at parity with exome-seq for variant detection in the targeted coding regions. WGS offers benefits in uniformity of read coverage and more balanced allele ratio calls, both of which can in most cases be offset by deeper exome-seq, with the caveat that some exome-seq targets will never achieve sufficient mapped read depth for variant detection due to technical difficulties or probe failures. As WGS is intrinsically richer data that can provide insight into polymorphisms outside coding regions and reveal genomic rearrangements, it is likely to progressively replace exome-seq for many applications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-247) contains supplementary material, which is available to authorized users

Mapping the human cortical surface by combining quantitative T(1) with retinotopy

We combined quantitative relaxation rate (R1= 1/T1) mapping-to measure local myelination-with fMRI-based retinotopy. Gray-white and pial surfaces were reconstructed and used to sample R1 at different cortical depths. Like myelination, R1 decreased from deeper to superficial layers. R1 decreased passing from V1 and MT, to immediately surrounding areas, then to the angular gyrus. High R1 was correlated across the cortex with convex local curvature so the data was first "de-curved". By overlaying R1 and retinotopic maps, we found that many visual area borders were associated with significant R1 increases including V1, V3A, MT, V6, V6A, V8/VO1, FST, and VIP. Surprisingly, retinotopic MT occupied only the posterior portion of an oval-shaped lateral occipital R1 maximum. R1 maps were reproducible within individuals and comparable between subjects without intensity normalization, enabling multi-center studies of development, aging, and disease progression, and structure/function mapping in other modalities

Quantifying single nucleotide variant detection sensitivity in exome sequencing

BACKGROUND: The targeted capture and sequencing of genomic regions has rapidly demonstrated its utility in genetic studies. Inherent in this technology is considerable heterogeneity of target coverage and this is expected to systematically impact our sensitivity to detect genuine polymorphisms. To fully interpret the polymorphisms identified in a genetic study it is often essential to both detect polymorphisms and to understand where and with what probability real polymorphisms may have been missed. RESULTS: Using down-sampling of 30 deeply sequenced exomes and a set of gold-standard single nucleotide variant (SNV) genotype calls for each sample, we developed an empirical model relating the read depth at a polymorphic site to the probability of calling the correct genotype at that site. We find that measured sensitivity in SNV detection is substantially worse than that predicted from the naive expectation of sampling from a binomial. This calibrated model allows us to produce single nucleotide resolution SNV sensitivity estimates which can be merged to give summary sensitivity measures for any arbitrary partition of the target sequences (nucleotide, exon, gene, pathway, exome). These metrics are directly comparable between platforms and can be combined between samples to give “power estimates” for an entire study. We estimate a local read depth of 13X is required to detect the alleles and genotype of a heterozygous SNV 95% of the time, but only 3X for a homozygous SNV. At a mean on-target read depth of 20X, commonly used for rare disease exome sequencing studies, we predict 5–15% of heterozygous and 1–4% of homozygous SNVs in the targeted regions will be missed. CONCLUSIONS: Non-reference alleles in the heterozygote state have a high chance of being missed when commonly applied read coverage thresholds are used despite the widely held assumption that there is good polymorphism detection at these coverage levels. Such alleles are likely to be of functional importance in population based studies of rare diseases, somatic mutations in cancer and explaining the “missing heritability” of quantitative traits

Gorham-Stout case report: a multi-omic analysis reveals recurrent fusions as new potential drivers of the disease

BACKGROUND: Gorham-Stout disease is a rare condition characterized by vascular proliferation and the massive destruction of bone tissue. With less than 400 cases in the literature of Gorham-Stout syndrome, we performed a unique study combining whole-genome sequencing and RNA-Seq to probe the genomic features and differentially expressed pathways of a presented case, revealing new possible drivers and biomarkers of the disease. CASE PRESENTATION: We present a case report of a white 45-year-old female patient with marked bone loss of the left humerus associated with vascular proliferation, diagnosed with Gorham-Stout disease. The analysis of whole-genome sequencing showed a dominance of large structural DNA rearrangements. Particularly, rearrangements in chromosomes seven, twelve, and twenty could contribute to the development of the disease, especially a gene fusion involving ATG101 that could affect macroautophagy. The study of RNA-sequencing data from the patient uncovered the PI3K/AKT/mTOR pathway as the most affected signaling cascade in the Gorham-Stout lesional tissue. Furthermore, M2 macrophage infiltration was detected using immunohistochemical staining and confirmed by deconvolution of the RNA-seq expression data. CONCLUSIONS: The way that DNA and RNA aberrations lead to Gorham-Stout disease is poorly understood due to the limited number of studies focusing on this rare disease. Our study provides the first glimpse into this facet of the disease, exposing new possible therapeutic targets and facilitating the clinicopathological diagnosis of Gorham-Stout disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01277-x

Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification

Endometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER−) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR−/ER + , PR−/ER−) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04–0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14–5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours—which are typically CTNNB1-mutant and TP53 wild-type—experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy